SCEHSC Seminar Series with Dave Conti, PhD

Title: The Interface of Polygenic Risk Scores, Non-genetic Factors, and Populations

Guest Speaker: Dave Conti, PhD

There are stark differences in the burden of certain diseases across populations. For example, in comparison to individuals of European ancestry, African American men have a ~67% higher incidence rate of prostate cancer and Asian/Pacific Islander men and women have a 70% and 95% higher incidence rate of liver cancer, respectively. These disparities in the burden of disease have been attributed to an interplay of genetic, environmental, and social factors. Despite such disparities, a majority of genetic research has focused on individuals of European ancestry. The inadequate representation of diverse populations limits the translational potential of genetic findings to all individuals. This is especially true for the application of polygenic risk scores (PRS), indices that summarize the genetic impact on a disease or complex trait. Applying PRS developed in European ancestry individuals to other populations may result in biased risk prediction, and further exacerbate health disparities due to inaccurate assessment of individuals at high risk of disease. In this talk, I will discuss research that we have been performing to address the drastic need for appropriate PRS implementation across populations. This research utilizes more diverse datasets and applies novel statistical approaches for construction and evaluation. I will highlight issues in using joint models for integrating PRS and non-genetic factors (e.g. environmental exposures and/or social determinants of health) to estimate absolute risk in diverse populations. Topics include challenges in defining baseline risk, application to admixed individuals, and the careful and deliberate use of population descriptors, following recent recommendations from the National Academies of Sciences, Engineering, and Medicine.